rs1970121

chr9-92107870-C-Achr9-92107870-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006415.4(SPTLC1):c.260+870G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,084 control chromosomes in the GnomAD database, including 9,627 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (9627 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPTLC1 NM_006415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

Genes affected

SPTLC1 (HGNC:11277): (serine palmitoyltransferase long chain base subunit 1) This gene encodes a member of the class-II pyridoxal-phosphate-dependent aminotransferase family. The encoded protein is the long chain base subunit 1 of serine palmitoyltransferase. Serine palmitoyltransferase converts L-serine and palmitoyl-CoA to 3-oxosphinganine with pyridoxal 5'-phosphate and is the key enzyme in sphingolipid biosynthesis. Mutations in this gene were identified in patients with hereditary sensory neuropathy type 1. Alternatively spliced variants encoding different isoforms have been identified. Pseudogenes of this gene have been defined on chromosomes 1, 6, 10, and 13. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTLC1	NM_006415.4	c.260+870G>T		intron_variant		ENST00000262554.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTLC1	ENST00000262554.7	c.260+870G>T		intron_variant		1	NM_006415.4	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46449 AN: 151966 Hom.: 9596 Cov.: 33

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.284

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.306 AC: 46533 AN: 152084 Hom.: 9627 Cov.: 33 AF XY: 0.307 AC XY: 22799 AN XY: 74370

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.289

Alfa AF: 0.242 Hom.: 930

Bravo AF: 0.327

Asia WGS AF: 0.354 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.82
Dann	Benign	0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1970121; hg19: chr9-94870152;